MicroRNA miR-146a and further oncogenesis-related cellular microRNAs are dysregulated in HTLV-1-transformed T lymphocytes

• Main Authors: Schneider Grit, Pichler Klemens, Grassmann Ralph
• Format: Article
• Language: English
• Published: BMC 2008-11-01
• Series: Retrovirology
• Online Access: http://www.retrovirology.com/content/5/1/100

<p>Abstract</p> <p>Background</p> <p>Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of a severe and fatal lymphoproliferative disease of mainly CD4⁺T cell origin, adult T cell leukemia, which develops after prolonged viral persistence. Transformation of infected cells involves HTLV-1's oncoprotein Tax, which perturbs cell cycle regulation and modulates cellular gene expression. The latter function is also a hallmark of microRNAs, a rather new layer in the regulation of gene expression. Affecting e.g. proliferation, microRNAs constitute a potential target for viral interference on the way to persistence and transformation. Hence, we explored the interconnections between HTLV-1 and cellular microRNAs.</p> <p>Results</p> <p>We report that several microRNAs – miRs 21, 24, 146a, 155 and 223 – are deregulated in HTLV-1-transformed cells. They are all upregulated except for miR-223, which is downregulated. Each of those microRNAs has ties to cancer. Their expression pattern forms a uniform phenotype among HTLV-transformed cells when compared to HTLV-negative control cells. In particular, miR-146a expression was found to be directly stimulated by Tax via NF-<it>κ</it>B-mediated transactivation of its promoter; a single NF-<it>κ</it>B site proximal to the transcription start point was necessary and sufficient for this to happen. An <it>in silico </it>analysis of potential target genes revealed candidates that might be coregulated by two or more of the aforementioned overexpressed microRNAs.</p> <p>Conclusion</p> <p>These data demonstrate that cellular microRNAs are deregulated in HTLV-1-transformed T cells. In the case of miR-146a, this could be directly attributed to HTLV's oncoprotein Tax. Interference with cellular microRNAs may be crucial to maintaining persistence or may facilitate transformation of host cells.</p>